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基于体细胞突变谱整合的乳腺癌患者分层的结构深度聚类网络

英文原题:Structural deep clustering network for stratification of breast cancer patients through integration of somatic mutation profiles.

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Structural deep clustering network for stratification of breast cancer patients through integration of somatic mutation profiles.

PubMed 2023/09/12(内容时间) Comput Methods Programs Biomed Q1 · IF 6.4(JCR 2025)

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研究概要

我们的研究代表了朝着仅使用体细胞突变数据和结构深度聚类网络方法对癌症患者进行分类的通用方法学迈出的一步。采用结构深度聚类网络识别乳腺癌亚型具有前景,并可为开发更准确和个性化的疗法提供信息。

研究思路结论见上方概要

乳腺癌是女性中最常见的恶性肿瘤之一,也是全球妇科恶性肿瘤致死的主要原因之一。乳腺癌的高度异质性使得制定有效的治疗策略具有挑战性。越来越多的证据强调了将乳腺癌患者分为具有临床意义的亚型以实现更好的预后和治疗的关键作用。结构深度聚类网络是一种基于图卷积网络的聚类算法,它整合了结构信息,并在各种应用中取得了最先进的性能。

在本研究中,我们采用结构深度聚类网络整合体细胞突变谱,将来自纪念斯隆-凯特琳癌症中心的2526名乳腺癌患者分为两个临床可区分的亚型。

聚类1的乳腺癌患者预后优于聚类2的乳腺癌患者,两者差异具有统计学意义。免疫基因组图谱进一步表明,聚类1与TIL(肿瘤浸润淋巴细胞)的显著浸润相关。该聚类亚型可用于评估乳腺癌患者免疫治疗和化疗的治疗获益。此外,我们的方法有效地对来自八种不同癌症类型的患者进行了分类,证明了其普适性。

展开英文摘要原文

Breast cancer is among of the most malignant tumor that occurs in women and is one of the leading causes of death from gynecologic malignancy worldwide. The high degree of heterogeneity that characterizes breast cancer makes it challenging to devise effective therapeutic strategies. Accumulating evidence highlights the crucial role of stratifying breast cancer patients into clinically significant subtypes to achieve better prognoses and treatments. The structural deep clustering network is a graph convolutional network-based clustering algorithm that integrates structural information and has achieved state-of-the-art performance in various applications.

In this study, we employed structural deep clustering network to integrate somatic mutation profiles for stratifying 2526 breast cancer patients from the Memorial Sloan Kettering Cancer Center into two clinically differentiable subtypes.

Breast cancer patients in cluster 1 exhibited better prognosis than breast cancer patients in cluster 2, and the difference between them was statistically significant. The immunogenomic landscape further demonstrated that cluster 1 was associated with remarkable infiltration of the tumor infiltrating lymphocytes. The clustering subtype could be used to evaluate the therapeutic benefit of immunotherapy and chemotherapy in breast cancer patients. Furthermore, our approach effectively classified patients from eight different cancer types, demonstrating its generalizability.

Our study represents a step towards a generic methodology for classifying cancer patients using only somatic mutation data and structural deep clustering network approaches. Employing structural deep clustering network to identify breast cancer subtypes is promising and can inform the development of more accurate and personalized therapies.

论文信息

作者
Su D、Xiong Y、Wang S、Wei H、Ke J、Li H、Wang T、Zuo Y
第一作者单位
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.China
通讯作者单位
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China. Electronic address: leiyang@hrbmu.edu.cn.China
期刊
Computer methods and programs in biomedicine2023 Dec
原文标识
PubMed 37716222 · DOI 10.1016/j.cmpb.2023.107808